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Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel

Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-...

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Main Authors: Aryal, Prafulla, Abd. Wahab, Mohd. Firdaus, Bucci, Giovanna, Sansom, Mark S.P., Tucker, Stephen J.
Format: Article
Language:English
Published: Taylor and Francis Group, LLC 2015
Subjects:
Q Science (General)
QP Physiology
Online Access:http://irep.iium.edu.my/50082/1/50082.pdf
http://irep.iium.edu.my/50082/
http://www.tandfonline.com/doi/full/10.4161/19336950.2014.981987
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spelling my.iium.irep.500822016-05-22T19:28:58Z http://irep.iium.edu.my/50082/ Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel Aryal, Prafulla Abd. Wahab, Mohd. Firdaus Bucci, Giovanna Sansom, Mark S.P. Tucker, Stephen J. Q Science (General) QP Physiology Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets can occupy the fenestrations and partially penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity. Taylor and Francis Group, LLC 2015-01 Article REM application/pdf en http://irep.iium.edu.my/50082/1/50082.pdf Aryal, Prafulla and Abd. Wahab, Mohd. Firdaus and Bucci, Giovanna and Sansom, Mark S.P. and Tucker, Stephen J. (2015) Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel. Channels, 9 (1). pp. 44-49. ISSN 1933-6950 http://www.tandfonline.com/doi/full/10.4161/19336950.2014.981987 10.4161/19336950.2014.981987
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
topic Q Science (General)
QP Physiology
spellingShingle Q Science (General)
QP Physiology
Aryal, Prafulla
Abd. Wahab, Mohd. Firdaus
Bucci, Giovanna
Sansom, Mark S.P.
Tucker, Stephen J.
Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
description Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets can occupy the fenestrations and partially penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity.
format Article
author Aryal, Prafulla
Abd. Wahab, Mohd. Firdaus
Bucci, Giovanna
Sansom, Mark S.P.
Tucker, Stephen J.
author_facet Aryal, Prafulla
Abd. Wahab, Mohd. Firdaus
Bucci, Giovanna
Sansom, Mark S.P.
Tucker, Stephen J.
author_sort Aryal, Prafulla
title Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_short Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_full Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_fullStr Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_full_unstemmed Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
title_sort influence of lipids on the hydrophobic barrier within the pore of the twik-1 k2p channel
publisher Taylor and Francis Group, LLC
publishDate 2015
url http://irep.iium.edu.my/50082/1/50082.pdf
http://irep.iium.edu.my/50082/
http://www.tandfonline.com/doi/full/10.4161/19336950.2014.981987
_version_ 1643613657918078976
score 13.211869

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